Rahway, New Jersey, United States, November 9, 2026
Merck & Co., Inc. has announced positive results from its Phase 2b clinical trial evaluating efinopegdutide, an investigational once-weekly injectable therapy, in adults with metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-advanced liver fibrosis. The study demonstrated statistically significant improvements in MASH resolution without worsening of liver fibrosis compared with placebo after 52 weeks of treatment. The findings were presented during a late-breaking session at The Liver Meeting 2026 in Denver, Colorado, and simultaneously published in The Lancet. Efinopegdutide is a dual GLP-1 and glucagon receptor co-agonist designed to address metabolic dysfunction and liver fat accumulation through complementary biological mechanisms. The Phase 2b study evaluated three weekly doses of the candidate and found that 56% to 63% of participants achieved MASH resolution without worsening fibrosis, compared with 13% receiving placebo. Improvements were also observed in liver fibrosis without worsening steatohepatitis, an important secondary histological endpoint. These findings add to the growing clinical research into targeted treatments for MASH, a progressive liver disease associated with metabolic dysfunction, inflammation and potential progression to cirrhosis.
Phase 2b Trial Achieves Primary MASH Endpoint
The Phase 2b MK-6024-013 clinical trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy, safety and tolerability of efinopegdutide in adults with biopsy-confirmed MASH and stage F2 or F3 liver fibrosis. A total of 386 participants were enrolled, with 381 randomized and receiving at least one dose of study treatment. Participants received once-weekly subcutaneous efinopegdutide at doses of 4 mg, 7 mg or 10 mg, placebo, or an open-label active reference treatment with semaglutide 2.4 mg. The primary endpoint measured the proportion of participants achieving MASH resolution without worsening of fibrosis at Week 52, based on liver biopsy assessments using the NASH Clinical Research Network scoring system and blinded independent central review. The results showed that 56% of participants receiving the 4 mg dose achieved the primary endpoint, compared with 63% in the 7 mg group and 61% in the 10 mg group. In contrast, only 13% of participants receiving placebo achieved MASH resolution without worsening fibrosis. All three efinopegdutide dose groups demonstrated statistically significant differences compared with placebo, with p-values below 0.0001. These findings indicate a meaningful treatment response across the evaluated doses and establish that the study met its primary efficacy objective.
Liver Fibrosis Improvements and Safety Findings
Beyond MASH resolution, the study evaluated whether efinopegdutide could improve liver fibrosis without worsening steatohepatitis. Fibrosis is the accumulation of scar tissue resulting from chronic liver injury and inflammation, and its progression can eventually lead to cirrhosis and liver failure. At Week 52, at least one-stage improvement in fibrosis without worsening steatohepatitis was observed in 43% of participants receiving 4 mg, 52% receiving 7 mg and 34% receiving 10 mg. The corresponding response rate in the placebo group was 21%. These findings provide additional evidence of potential benefits beyond reducing liver inflammation and achieving disease resolution. The safety profile was generally consistent with the known profile of semaglutide, although gastrointestinal adverse events were commonly reported. Nausea occurred in 29%, 39% and 44% of participants receiving efinopegdutide at 4 mg, 7 mg and 10 mg, respectively, compared with 39% in the semaglutide group and 11% with placebo. Diarrhea and vomiting were also reported across the treatment groups. Discontinuations due to adverse events occurred in 3%, 4% and 11% of participants in the respective efinopegdutide dose groups, compared with 1% in both the semaglutide and placebo groups. These safety findings will require further evaluation in larger and longer clinical studies.
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Dual Receptor Approach Advances MASH Research
Efinopegdutide, also known as MK-6024, is designed to activate both glucagon-like peptide-1 (GLP-1) and glucagon receptors. GLP-1 receptor activation contributes to appetite regulation and metabolic control, while glucagon receptor activation is intended to support increased energy expenditure, lipid metabolism and direct effects on liver fat accumulation. By combining these mechanisms, Merck aims to develop a treatment capable of addressing multiple metabolic processes involved in MASH. The candidate has received U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of MASH, reflecting the need for additional therapeutic options for patients with this progressive condition. Efinopegdutide is being developed under an exclusive licensing agreement between Merck and Hanmi Pharmaceutical. MASH, previously known as non-alcoholic steatohepatitis (NASH), is a serious form of metabolic dysfunction-associated steatotic liver disease (MASLD), characterized by excess liver fat, inflammation and hepatocellular injury. The Phase 2b results represent an important clinical milestone, but efinopegdutide remains investigational and has not been approved for MASH. Further development and regulatory evaluation will be necessary to establish its long-term efficacy and safety.
Source: Merck press release
